The mechanical environment of the chondrocytes is an important factor that affects the health and function of the diarthrodial joint. The biomechanical and physicochemical signals to which chondrocytes are exposed depend on the interactions between the cell, pericellular matrix, and extracellular matrix of articular cartilage. The goals of this study are to measure the intrinsic biomechanical, physicochemical, and diffusion properties of the chondrocyte pericellular matrix, and to test the hypothesis that these properties are altered in osteoarthritic cartilage. Furthermore, we propose that type VI collagen, which is abundantly present in the pericellular matrix, influences the physical properties of this region. We will use several novel micromechanical experimental techniques in combination with theoretical modeling to quantify the triphasic mechanical properties of the pericellular matrix in the isolated chondron model and in transgenic mice. The aims of this project are to measure the triphasic mechanical properties of the pericellular matrix from normal and osteoarthritic cartilage using atomic force microscopy, incorporate these findings in a theoretical triphasic model of cell-matrix interactions in cartilage, and validate these predictions using confocal microscopy. We will also use new fluorescence-based methods to measure the diffusion properties of the pericellular matrix of normal and OA cartilage. Finally, we will determine the role of type VI collagen on the triphasic mechanical properties of the pericellular matrix and subsequently, the mechanical environment of the chondrocyte. The long-term goals of this study are to improve our understanding of the role of mechanical factors in the regulation of cartilage metabolism in normal and diseased conditions. A better understanding of these pathways will hopefully lead to the development of new pharmaceutical or biophysical interventions for the treatment of osteoarthritis. PUBLIC HEALTH RELEVANCE: The goals of this study are to measure the intrinsic biomechanical, physicochemical, and diffusion properties of the chondrocyte pericellular matrix, and to test the hypothesis that these properties are altered in osteoarthritic cartilage. Furthermore, we propose that type VI collagen, which is abundantly present in the pericellular matrix, influences the physical properties of this region. We will use several novel micromechanical experimental techniques, coupled with theoretical modeling to quantify the triphasic mechanical properties of the pericellular matrix and to determine the influence of this region on the physicochemical environment of the chondrocyte in health and disease.